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Novel Indole-Pyrazole Hybrids as Potential Tubulin-Targeting Agents; Synthesis, antiproliferative evaluation, and molecular modeling studies

  1. Author:
    Hawash, Mohammed
    Ergun, Sezen Guntekin
    Kahraman, Deniz Cansen
    Olgac, Abdurrahman
    Hamel,Ernest
    Cetin-Atalay, Rengul
    Baytas, Sultan Nacak

  2. Author Address

    Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Gazi University, 06330, Ankara, Turkey., Department of Pharmacy, Faculty of Medicine and Health Sciences, An-Najah National University, 00970, Nablus, Palestine., Cancer Systems Biology Laboratory, Graduate School of Informatics, Middle East Technical University, 06800, Ankara, Turkey., Department of Medical Biology, Hacettepe University, 06100, Ankara, Turkey., Molecular Pharmacology Branch, Developmental Therapeutics Program, Division of Cancer Treatment and Diagnosis, Frederick National Laboratory for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, Maryland 21702, USA.,
    1. Year: 2023
    2. Date: Aug 05
    3. Epub Date: 2023 03 31
  2. Journal: Journal of Molecular Structure
    1. 1285
  4. Type of Article: Article
  5. Article Number: 135477
  1. Abstract:

    Structurally diverse indole-3-pyrazole-5-carboxamide analogues (10-29) were designed, synthesized, and evaluated for their antiproliferative activity against three cancer cell lines (Huh7, MCF-7, and HCT116) using the sulforhodamine B assay. Some of the derivatives showed anticancer activities equal to or better than sorafenib against cancer cell lines. Compounds 18 showed potent activity against the hepatocellular cancer (HCC) cell lines, with IC50 values in the range 0.6-2.9 µM. Compound 18 also exhibited moderate inhibitory activity against tubulin polymerization (IC50 = 19 µM). Flow cytometric analysis of cultured cells treated with 18 also demonstrated that the compound caused cell cycle arrest at the G2/M phase in both Huh7 and Mahlavu cells and induced apoptotic cell death in HCC cells. Docking simulations were performed to determine possible modes of interaction between 18 and the colchicine site of tubulin and quantum mechanical calculations were performed to observe the electronic nature of 18 and to support docking results.

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External Sources

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  2. DOI: 10.1016/j.molstruc.2023.135477
  3. PMID: 37234266
  4. PMCID: PMC10208593
  5. PII : 135477

Library Notes

  1. Fiscal Year: FY2022-2023
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